Clinical Image

A 27 year-old woman presented to our muscle outpatient clinic accompanied by her foster parents.
She complained about generalized muscle weakness, modest weight loss, and an accompanying
depression; both had progressed over the past 2 years. Facioscapulohumeral dystrophy had been
diagnosed elsewhere. The parents had observed forgetfulness and a withdrawn behavior. The patient
was adopted making a family history impossible. She had successfully completed German secondary
schools, had enrolled at a university but had abandoned these plans to successfully complete a 3-year
apprenticeship. Nonetheless, she was currently unemployed. On examination, the right-handed
patient had no localizing neurological findings. Cranial nerves were not remarkable; speaking was
a little inarticulate. We detected no movement disorders. Trendelenburg and Romberg testing were
not specifically abnormal; however, gait- and-station appeared unstable. There was no specific
proximal or distal muscle weakness or signs of atrophy. We could not confirm the presence of
facioscapulohumeral dystrophy. Referring colleagues had expected a skeletal muscle disease, but
we could not settle on that diagnosis. Muscle stretch reflexes were non-localizing and there were
no pathological reflexes except brisk patellar and left-sided Achilles tendon reflex, but no Babinski
sign. We viewed the responses as less common for muscle disease and considered the likelihood of
a neurodegenerative disease. Depression still appeared possible, because of her withdrawn behavior,
lack of drive, loss of interest, and weight loss. However, her mood appeared appropriate and there
were no sleep disturbances. We performed clinical neuropsychological testing. The baseline minimental-
status-test gave 26 of a possible 30 points. An intelligence test based on vocabulary revealed
a normal score. The Hamilton depression scale was also nonspecific. The patient was cooperative
and motivated. Her speech was fluid and appropriate. However, her memory and repetition skills
seemed impaired, she occasionally perseverated, and appeared slightly dysarthric. In the clock
completion test (Figure 1A), she required corrections and constructed the clock hands as a single
line. The Trail-making Test and the requirement to alternate between numbers and letters were
slowed and not without errors. When attempting to achieve a certain number or letter she often
did not achieve her aim but instead performed these tests with quick spontaneous correction loops
(Figure 1B and 1C). We were uncomfortable with the diagnoses of skeletal-muscle and depressive
disorders. We considered the possibility of a neurodegenerative disease, including Huntington’s
disease. However, generally that diagnosis does not rest on solely psychological symptoms. Our
psychiatric consultant regarded that diagnosis as unlikely.
Analysis of CAG repeats at the HTT locus on chromosome 4p revealed 14 CAG repeats on
one allele and 53 CAG repeats on the other. CAG is the triplet codon for glutamine. A series of
glutamines results in a polyglutamine tract (polyQ tract). Generally, persons have fewer than 36
CAG repeats. More than this number alters the characteristic of the Huntingtin protein resulting in
the neurodegenerative condition termed Huntington’s disease [1]. We obtained additional relevant
history contact with both biological parents and four siblings had been lost. The patient was always petit but had been athletic as a child and loved her bicycle. For two
years, she had been unable to ride because of difficulties maintaining
her balance. She reported falling frequently but was able to get up
unassisted. Since she had received neurological care elsewhere, we
inquired about imaging. An earlier brain magnetic resonance imaging
study had been performed. In retrospect, very small alterations
in the corpus striatum were identified (appendix). Huntington’s
disease is an autosomal-dominant genetic disorder affecting muscle
coordination, leading to mental decline and behavioral symptoms
[1]. The condition generally becomes symptomatic beyond 35 years;
however, 6% of cases begin prior to 21 years. Our patient exhibited
subtle changes in mood and cognition [2]. In retrospect, a general
lack of coordination was apparent. Our patient showed no clear
movement disorder, which probably led to a delay in diagnosis.
We have counseled our patient and her foster parents, who gave us
consent to report her findings. Unfortunately, there is no approved
treatment for Huntington’s disease. Histone deacetylase (HDAC) [4] is a transcriptional repressor containing a glutamine-rich domain
could possibly be developed as a therapeutic target [3]. Even green
tea has shown some promise [4]. Our patient underscores the role of clinical-pattern building and thorough testing when confronting
unusual psychiatric presentations of genetic conditions.